Development and validation of the antibody-dependent cellular phagocytosis-based signature: A prognostic risk model of gastric cancer

Adv Clin Exp Med. 2024 Nov 18. doi: 10.17219/acem/189914. Online ahead of print.

Abstract

Background: Accumulating evidence has supported the effect of antibody-dependent cellular phagocytosis (ADCP) on the tumor microenvironment (TME) and cancer therapy. However, an ADCP-based signature to predict the prognosis of gastric cancer (GC) has not been established.

Objectives: We aimed to develop an ADCP-based signature to improve the prognosis prediction of GC.

Material and methods: Antibody-dependent cellular phagocytosis genes that exhibited a differential expression were characterized, followed by the construction and validation of the ADCP-based signature. The potential association between the ADCP-based signature and TME was explored, and the features of the signature genes were investigated. Finally, a predictive nomogram was established based on the ADCP-based signature.

Results: Four ADCP-related genes, MKNK2, VCAN, LRAT, and GNGB, were identified to construct the ADCP-based signature, and a high ADCP score predicted an unfavorable prognosis in GC patients (p < 0.05). The ADCP-based signature was significantly associated with immune cells, immune checkpoints and immune signaling pathways (p < 0.05). Gastric cancer patients with high ADCP scores benefited less from immunotherapy compared to those with low ADCP scores. A nomogram including age, stage and risk score of the ADCP-based signature was constructed to predict the 1-, 3- and 5-year survival probabilities, with an area under the curve (AUC) of 0.669, 0.675 and 0.685, respectively.

Conclusions: The ADCP-based signature may serve as a new option for prognosis prediction and the personalized treatment of GC patients.

Keywords: antibody-dependent cellular phagocytosis; bioinformatics analysis; gastric cancer; prognostic signature; tumor microenvironment.